【摘要】：目的:精神分裂癥是一種病因及發(fā)病機(jī)制未明的慢性重型精神疾病,除神經(jīng)遞質(zhì)假說外,還可能與神經(jīng)營養(yǎng)及神經(jīng)損傷有關(guān),炎性反應(yīng)也可能在精神類疾病發(fā)展中起重要作用,尤其與精神分裂癥的發(fā)生存在顯著的相關(guān)性。精神分裂癥進(jìn)展過程中常常伴隨著認(rèn)知功能受損,嚴(yán)重影響精神分裂癥患者的預(yù)后,成為公認(rèn)的重大公共衛(wèi)生難題。研究表明,小檗堿具有拮抗氧化應(yīng)激,抑制炎癥反應(yīng)的作用。動(dòng)物實(shí)驗(yàn)表明,它還具有保護(hù)神經(jīng)細(xì)胞,改善學(xué)習(xí)記憶功能等作用。然而這一作用僅限于動(dòng)物研究水平,臨床研究未見報(bào)道。本課題探討小檗堿對(duì)精神分裂癥患者血清BDNF、CRP水平及認(rèn)知功能的影響及其可能作用機(jī)制,為進(jìn)一步探討精神分裂癥的發(fā)病機(jī)理,尋找新的治療方法提供線索。方法:本研究采用隨機(jī)雙盲、安慰劑對(duì)照的研究方法,根據(jù)DSM-V關(guān)于精神分裂癥的診斷標(biāo)準(zhǔn)選取精神分裂癥住院患者64名,所有入組的受試者均使用利培酮單藥治療。隨機(jī)將患者分為研究組與對(duì)照組,兩組性別、年齡均相匹配,且維持入組時(shí)利培酮治療劑量。研究組用藥為利培酮合并小檗堿(300 mg TID)治療,對(duì)照組用藥為利培酮合并小檗堿安慰劑治療,治療周期為12周。受試者在第0周入組時(shí)進(jìn)行基線測驗(yàn),測量基線血清BDNF及CRP水平,進(jìn)行認(rèn)知功能測評(píng),包括連線測驗(yàn)(TMTA)、符號(hào)編碼測驗(yàn)(SC)、流暢性、迷宮測驗(yàn)、情緒智商測驗(yàn)、PSP量表評(píng)分。在研究的第12周末,重復(fù)上述測定內(nèi)容,比較治療前后上述指標(biāo)的差異水平,評(píng)估小檗堿對(duì)精神分裂癥患者血清BDNF、CRP水平及認(rèn)知功能的影響。數(shù)據(jù)結(jié)果分析采用SPSS17.0統(tǒng)計(jì)軟件包進(jìn)行,P值小于0.05為差異具有顯著性。結(jié)果:1、與基線相比,研究組血清BDNF水平在第12周末的差異具有統(tǒng)計(jì)學(xué)意義(P0.01);治療后組間比較,研究組和對(duì)照組BDNF水平的差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。2、與基線相比,研究組CRP水平在第12周末的差異具有統(tǒng)計(jì)學(xué)意義(P0.01);治療后組間比較,研究組和對(duì)照組CRP水平的差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。3、治療12周末與基線相比,研究組在處理速度維度各項(xiàng)目、迷宮測驗(yàn)、情緒智商測驗(yàn)均有顯著改善(P0.01);治療后組間比較,研究組和對(duì)照組處理速度維度各項(xiàng)目粗分、情緒智商測驗(yàn)差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。4、治療12周末與基線相比,研究組社會(huì)中有益的活動(dòng)、個(gè)人關(guān)系和社會(huì)關(guān)系、自我照料、擾亂及攻擊行為、PSP總分的差異具有統(tǒng)計(jì)學(xué)意義(P0.05);治療后組間比較,研究組和對(duì)照組社會(huì)中有益的活動(dòng)評(píng)分具有顯著差異(P0.05)。結(jié)論:1、小檗堿可升高利培酮單藥治療的精神分裂癥患者血清BDNF水平,具有神經(jīng)保護(hù)作用。2、小檗堿可降低利培酮單藥治療的精神分裂癥患者CRP水平,抑制炎癥反應(yīng)。3、小檗堿可顯著改善利培酮治療精神分裂癥患者認(rèn)知功能,對(duì)信息處理速度、社會(huì)認(rèn)知、工作學(xué)習(xí)能力有改善作用,而對(duì)患者的執(zhí)行功能并無改善作用。
[Abstract]:Objective: schizophrenia is a chronic severe mental disease with unknown etiology and pathogenesis. In addition to the neurotransmitter hypothesis, it may also be related to neurotrophic and nerve injury. Inflammatory reaction may also play an important role in the development of mental diseases. In particular, there is a significant correlation with the occurrence of schizophrenia. Cognitive impairment is often associated with the progression of schizophrenia, which seriously affects the prognosis of patients with schizophrenia and has become a recognized major public health problem. The results showed that berberine could antagonize oxidative stress and inhibit inflammatory reaction. Animal experiments show that it can also protect nerve cells and improve learning and memory function. However, this effect is limited to animal research level, clinical studies have not been reported. The purpose of this study was to investigate the effect of berberine on serum BDNF,CRP level and cognitive function and its possible mechanism in schizophrenic patients, and to provide clues for further exploring the pathogenesis of schizophrenia and finding new treatment methods. Methods: a randomized, double-blind, placebo-controlled study was conducted to select 64 schizophrenic inpatients according to DSM-V 's criteria for schizophrenia. All subjects were treated with risperidone alone. The patients were randomly divided into study group and control group. The study group was treated with risperidone combined with berberine (300 mg TID), the control group was treated with risperidone and berberine placebo for 12 weeks. At week 0, baseline test was performed, baseline serum BDNF and CRP levels were measured, and cognitive function was evaluated, including (SC), fluency, maze test and emotional intelligence quotient test (EIQ). At the end of the 12th week of the study, the above measurement was repeated to compare the difference of the above indexes before and after treatment, and to evaluate the effect of berberine on serum BDNF,CRP level and cognitive function in schizophrenic patients. Data analysis using SPSS17.0 statistical software package for P < 0. 05 had significant difference. Results compared with the baseline, the serum BDNF level of the study group was significantly different from that of the baseline (P0.01), and the difference between the study group and the control group was statistically significant after treatment (P0.05) .2Compared with the baseline. The difference of CRP level in the study group at the 12th weekend was statistically significant (P0.01); after treatment, the difference of CRP level between the study group and the control group was statistically significant (P0.05) .3.Compared with the baseline at the end of the 12th week, the study group was in each item of processing speed dimension. Labyrinth test and emotional IQ test were significantly improved (P0.01). After treatment, there were significant differences between the study group and the control group in the processing speed dimension of each item coarse score, emotional IQ test difference was statistically significant (P0.05) .4, 12 weeks after treatment compared with the baseline, There were statistically significant differences in the total scores of beneficial activities, personal relationships and social relations, self-care, disturbance and aggression in the study group (P0.05). There was significant difference in the score of beneficial activities between the study group and the control group (P0.05). Conclusion berberine can increase the level of serum BDNF in schizophrenic patients treated with risperidone, and has neuroprotective effect. Berberine can decrease the level of CRP in patients with schizophrenia treated with risperidone alone. Inhibition of inflammatory response. 3. Berberine can significantly improve the cognitive function of patients with schizophrenia treated with risperidone. It can improve the speed of information processing, social cognition and working and learning ability, but has no effect on the executive function of the patients.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R749.3

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